title: Effect of prostaglandin e2 on vascular endothelial growth factor production in nasal polyp fibroblasts.
abstract: OBJECTIVE
  Angiogenesis is involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. We aimed to investigate the effects of prostaglandin E2 (PGE2) on vascular endothelial growth factor (VEGF) production, the role of E-prostanoid (EP) 4 receptors, and the signal transduction pathway mediating VEGF production in nasal polyp-derived fibroblasts (NPDFs).
  
  
  METHODS
  Eight primary NPDF cultures were established from nasal polyps, which were incubated with or without PGE2. Reverse transcription-polymerase chain reaction amplification of EP receptors (EP1, EP2, EP3, and EP4) and immunofluorescence staining for VEGF production were performed. VEGF production via the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI3K) pathways was evaluated by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  All EP receptors were expressed in NPDFs. PGE2 significantly increased VEGF production concentration- and time dependently, and VEGF production was regulated by an EP4 receptor. Activation of intracellular cAMP regulated VEGF production. VEGF production was decreased by PKA and PI3K inhibitors via intracellular cAMP.
  
  
  CONCLUSIONS
  PGE2 stimulates VEGF production via the EP4 receptor in NPDFs. These results indicate that PGE2-induced VEGF production is mediated, at least partially, through cAMP-dependent signaling pathways. Therapies targeting the EP4 receptor may be effective in inhibiting the development of nasal polyps.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan, Korea.
authors.forename: Dong Yeol
authors.initials: DY
authors.lastname: Han
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Cho
authors.forename: You-Mi
authors.initials: YM
authors.lastname: Moon
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Lee
authors.forename: Heung-Man
authors.initials: HM
authors.lastname: Lee
authors.forename: Byung Don
authors.initials: BD
authors.lastname: Lee
authors.forename: Byoung Joon
authors.initials: BJ
authors.lastname: Baek
keywords: E-prostanoid receptor; Nasal polyp; cyclic adenosine monophosphate; fibroblast; prostaglandin E2; vascular endothelial growth factor